Epidemiology of primary brain tumor among adolescents and adults in Palestine: a retrospective study from 2018 to 2023

Backgrounds Primary brain tumors (PBTs) are uncommon, but they significantly increase the risk of disability and death. There is a deficiency of data concerning the epidemiology and anatomical distribution of PBTs among adults in Palestine. Methods A retrospective descriptive study in which data were collected from the clinical reports of Palestinian patients diagnosed with PBTs at Al-Makassed Hospital during the period (2018–2023). Results In Palestinian adolescents and adults, the incidence rate of PBTs was 3.92 per 100,000 person-years. Glioblastoma (18.8%) was the most common type identified, and it was more common in males. Non-malignant tumors were more common than malignant tumors (2.41 vs. 1.52 per 100,000). The mortality rate from PBTs was 4.8%. The most common initial symptom was headaches, and it occurred more with non-malignant tumors (57.28% vs. 42.72%, p-value < 0.001). Cerebral meninges (26.3%) were the most common location for primary brain tumors (p-value < 0.001). Conclusion This is the first study of primary brain tumor epidemiology in Palestine. The overall incidence of PBTs in Palestinian adolescents and adults was 3.96 per 100,000, which was lower than the incidence rate of primary brain tumors worldwide. More studies on the epidemiology and distribution of PBTs in Palestine are recommended.

chromosomes causes abnormal functioning, which in turn leads to the development of brain tumors.Usually, these genes' self-destruction systems help fix gene errors and regulate the rate at which cells divide [4].
PBTs are a broad category that includes a range of benign and malignant tumors that arise from different areas of the brain, including the skull base, meninges, cranial nerves, and the parenchyma [5,6].Over the decades, multiple studies have been implemented to determine the major risk factors contributing to the etiology of PBT; nevertheless, it is unclear which main risk factor accounts for a significant fraction of instances in the etiology of the brain and other central nervous system tumors [7].
PBTs are relatively rare, but they significantly increase the risk of disability and death.As a consequence, patients, their families, and the healthcare system bear a heavy burden [5].About 33.4% of PBTs survive for five years [8].In Palestine, in 2021, these tumors have contributed to roughly 5.7% of all cancer-related deaths [9].
Brain and other central nervous system (CNS) tumors constitute the 17th most prevalent type of cancer worldwide, contributing to 1.7% of all cancer cases (excluding non-melanoma skin cancer) [10].In 2015, PBTs comprised 7% and 6% of all cancer forms that affected males and females in Palestine respectively.In contrast, the rate of brain cancer as of 2020 was 3.1% for both sexes [9].Nevertheless, no such study provided reliable data on the types of these brain tumors, their epidemiology, clinical, anatomical, and histological presentations, and outcomes.
The epidemiologic features and anatomical distribution of adult PBTs are not well understood in Palestine.In this study, we aim to examine the incidence rate of adolescents and adult PBTs in Palestine in the last six years (2018-2023) and to determine their epidemiologic characteristics, histologic types, and anatomical distribution.

Study design and setting
Our study was a retrospective epidemiological descriptive study in which we collected data from the histopathology reports and MRI reports of Palestinian patients diagnosed with PBTs who were treated at Al-Makassed Hospital in Jerusalem, the largest tertiary referral center for PBTs in Palestine during the period (2018-2023).Our targeted population is patients diagnosed with PBTs who received healthcare at Al-Makassed Hospital in Jerusalem during this period.

Inclusion and exclusion criteria
Palestinian patients with PBTs aged 15 or more, whether diagnosed at Al-Makassed Hospital or referred to this hospital for treatment included in this study.Patients below the age of 15 years old, or with metastatic (secondary) brain tumors, spinal cord tumors, and those with missing histopathology reports or MRI reports were excluded.

Variables
The variables included in this study were the age at the time of diagnosis, sex (male or female), type of residency (city, village, or camp), anatomical location of the tumor in the brain as stated in the neuroradiology reports, type of the tumor on histopathology, and the behavior of the tumor (either benign, borderline, or malignant).The histopathological type of the tumor and its anatomical location within the brain were coded based on the third edition of the International Classification of Diseases of Oncology (ICD-O-3) Manual [11].The histopathological type and behavior of the tumor were coded in accordance with the 2016 WHO Classification for CNS tumors [12].

Data collection and tool
The main source of data collection was the clinical reports of patients for the sociodemographic data, the histopathology reports for the pathological type of the tumor, and the neuroimaging reports for the anatomical location of the tumor.The clinical reports and histopathology reports were obtained from the registry system at Al-Makassed Hospital.The population sizes for each year were obtained from the Palestinian Central Bureau of Statistics.The population size was used to calculate the crude incidence rate for each year.

Data analysis
The 26.0 version of the Statistical Package for Social Sciences (SPSS) was used in the analysis.For categorical and continuous variables, a basic descriptive analysis was performed.The incidence was calculated per 100,000.Chi-square tests and cross-tabulation were used for the analysis of the categorical variables.Statistical significance was set at 5%, and any p-value below 0.05 was considered statistically significant.

Sociodemographic characteristics of the patients
A total of 764 patients were diagnosed with PBTs during the period from 2018 to 2023.The patients exhibited a mean age of 44.58 years (SD ± 15.27).Females accounted for 53% of the total patients, whereas males constituted the remaining 47%.Geographically, about 49% of the patients were living in the major Palestinian cities, 44.1% in villages, and 6.9% in refugee camps.Regionally, 56.2% of the patients were from the West Bank and 43.8% from the Gaza Strip.The sociodemographic characteristics of the patients are presented in Table 1.

Incidence rate for PBTs by years and sex
During the period from 2018 to 2023, the annual incidence rate for PBTs ranged from 3.67 to 4.13, with an average annual incidence rate of 3.92.The overall incidence rate for 2018 was the highest, then abruptly declined to reach 3.89 in 2019, continued to gradually decrease until 2022, then increased to 4.13 in 2023.The average annual incidence rate for females was 4.21, higher than the average overall annual incidence rate (3.92) and the average annual incidence rate for males (3.64).The average annual male-to-female ratio was 0.86.Fig. 1 Annual Incidence rates of primary brain tumors per 100,000, classified by sex, for the period spanning from 2018 to 2023 The crude annual incidence rates for the PBTs are presented in Table 2 and illustrated in Fig. 1.

Distribution of cases in age groups and sex groups
About 20.8% of the patients were aged from 36 to 45 years, and 20.7% of them aged from 46 to 55 years.Patients aged from 15 to 25 years were about 12.6% of the total patients included in the study.The percentages of patients increase gradually from the 15-25 age group to the 36-45 age group, then gradually decrease to the 66-75 age group.Only 1% of the patients aged between 76 and 85 years.No significant differences between males and females in the different age groups were found.The distribution of cases in age groups is shown in Table 3 and illustrated in Fig. 2.

The behavior of the PBTs based on the WHO classification
About 48.56% of the total PBTs were benign, 38.61% of the tumors were malignant, and 12.83% of the tumors were unspecified, borderline, or uncertain behavior.The incidence rate of malignant tumors was 1.52 and the incidence rate of non-malignant tumors was 2.41.The percentage of malignant tumors was higher in males compared to females (p-value < 0.001), and in patients living in villages compared to patients living in cities and refugee camps (p-value = 0.037).Benign tumors were more likely to occur in female patients compared to male patients (p-value < 0.001), and patients living in villages compared to patients living in cities and refugee camps (p-value = 0.037).The behavior of the PBTs is shown in Table 4.
The anatomical locations of the PBTs are presented in Table 5 and illustrated in Fig. 3.

Distribution of the PBTs by histopathology
Diffuse astrocytic and oligodendroglial tumors were the most common histology group in our study with 252 cases (32.9%), followed by Meningiomas (26.4%), and tumors of the sellar region (19.1%).Glioblastoma was the most commonly identified histological type (18.8%), followed by pituitary adenoma (17.5%), and meningioma (16.5%).Among the malignant tumors, glioblastoma was the most common histologic type (48.8%).
Meningiomas accounted for 42.8% of the total nonmalignant tumors in our study, and pituitary adenoma accounted for 28.6% of them.Glioblastoma was more common in males (0.83 vs. 0.64, p-value < 0.001), while meningioma and pituitary adenoma were more common in females (0.35 vs. 0.94, and 0.65 vs. 0.73, respectively, p-value < 0.001).The distribution of PBTs by histopathology is presented in Table 6; Fig. 4.

First signs or symptoms for patients with PBTs
The most common first sign or symptom of PBTs among Palestinian patients was headache (41.4%), followed by focal signs (motor or sensory signs) (32.2%) and seizures (11%).The least common first signs or symptoms (0.1-0.7%) were dysarthria, neurogenic bladder/bowel, aphasia, and dysphagia.Among patients presenting first with focal signs, about 63.82% of them had a benign tumor,  and 26.02% of them had a malignant tumor.Table 7 presents the first signs or symptoms for patients with PBTs.

Mortality rate
The total mortality rate from PBTs was 4.8%.Mortality was significantly associated with the age groups only.
The mortality rate increases gradually from the 15-25 age group and reaches the highest level in the 76-85 age group.Despite their relatively rare occurrence, epitheliod glioblastoma, clear cell ependymoma, and solitary fibrous tumor were associated with 100% mortality rate.Medulloblastoma (large cell/ anaplastic) displayed the second highest mortality rate (50%), while both oligoastrocytoma and angiomatous meningioma had a mortality rate of 33% (p-value = 0.001).The mortality rate from primary brain tumors and its relation to sex, behavior of the tumor, histopathological types, and age groups is presented in Table 8.

Discussion
In many countries around the world, the incidence of PBTs and their subtypes is increasing and this could be explained by the raise in life expectancy of the population, increased access to healthcare, and availability of diagnostic imaging [13].
The mean age at diagnosis for the patients included in our study was 44.58 years (SD ± 15.27), which was lower than the mean age at diagnosis reported in previous studies in the USA [14], UK [15], France [16], and Lebanon [17], and higher than the mean age at diagnosis reported in a recent study in Jordan [6].Among adolescents and adult Palestinians, the average annual incidence rate was 3.92 per 100,000.The incidence rate of PBTs in Palestine was lower than the worldwide overall incidence rate (10.82 per 100,000) [5].When comparing the incidence rate in Palestine with the incidence rate in the Middle East, it was found to be lower than the incidence rate in Jordan (5.01 per 100,000) [6], and higher than the incidence rate in Qatar (2.2 per 100,000) and the UAE (0.56 per 100,000) [18,19].Moreover, the incidence rate of PBTs in Palestine was lower than the incidence rate in other countries like the USA (24.83 per 100,000) [14], Korea (23.39 per 100,000) [20], Austria (18.1 per 100,000) [21], Girona-Spain (16.85 per 100,000) [22], Georgia (10.62 per 100,000) [23], Lithuania (8 per 100,000), Norway (5.4 per 100,000), Australia (5.6 per 100,000), and Canada (5.3 per 100,000) [5].On the other hand, the incidence rate of PBTs in Palestine was higher than the estimated incidence rate of brain tumors in Mexico (2.7 per 100,000) [24].The gradual decrease in the incidence rate between 2020 and 2022 may be attributed to the COVID-19 pandemic, as during this period the transfer and admission rate for PBT decreased due to the movement restrictions and restricted entry to Jerusalem.The overall trend in the incidence of PBT needs further studies in the future to be determined.
The incidence rate in females was higher than in males.This result aligns with the findings of a previous study in Jordan [6].The male-to-female ratio in our study was slightly lower than the ratio in Austria and Georgia [21,23], and higher than Korea [20], UAE [19], and USA [14].We found that most of the patients (79%) were older than 25 years and younger than 66 years.No significant differences in age groups between the males and females were found (p-value = 0.352).The distribution of the percentage of patients in the age groups was similar to the findings reported in a study in Northeast India and Qatar [18,25].The malignant PBTs in our study were fewer than the non-malignant tumors (38.61% vs. 61.39%).This finding aligns with the findings reported in previous studies in the USA [14], Georgia [23], UAE [19], and Korea [20].Malignant tumors were more frequent than non-malignant tumors in Lebanon [17], England [15], and Spain [22].The incidence rate of malignant tumors in Palestinian adolescents and adults was lower than the incidence rate of non-malignant tumors (1.52 vs. 2.41 per 100,000).This finding aligns with the findings reported in previous studies in the USA [14], and Georgia [23].The incidence rate of malignant PBTs in Palestine was lower than the incidence rate of malignant tumors reported in the USA (6.94 per 100,000) [14], Korea (2.9 per 100,000) [20], and Iran (2.74 per 100,000) [26].
Meningiomas were the most common group of tumors identified in different studies around the world, including the USA (42.1%) [14], Korea (37.9%) [20], Lebanon (29.6%) [17], Northeast India [25], and Georgia [23], while in our study, the most common group of tumors identified in Palestinian adolescents and adults was diffuse astrocytic and oligodendroglial tumors (33%).In our study, the most commonly identified histopathological type was glioblastoma, while meningioma was the most common histopathological type identified in the USA [14], Korea [20], Jordan [6], Cameroon [27], and Austria [21].Cerebral meninges were the most common location for PBTs identified in our study (26.3%), a finding that is similar to the findings of recent studies in Lebanon [17] and the USA [14].Headaches, focal signs (motor or sensory signs), and seizures were the most common first signs or symptoms among Palestinian patients.These findings were similar to those reported in a recent study in Cameroon [27] and Saudi Arabia [28].
Unfortunately, no incidence rates of PBTs in Palestine during the years before 2018 were found in the literature, making the comparison and tracking the trend of annual incidence rates in Palestine impossible.We recommend conducting future studies that investigate the epidemiology of PBTs in Palestine including all the age groups of the population to provide constant information regarding the epidemiology of PBTs in Palestine.We also recommend using a unified methodology of similar epidemiological studies based on the WHO Classification of CNS tumors.

Conclusion
This is the first national study that investigates the epidemiology of PBTs in Palestine.The study was conducted in Al-Makassed Hospital in Jerusalem, which serves as the largest referral center for primary brain tumors in Palestine.The overall incidence of PBTs in Palestinian adolescents and adults was 3.96 per 100,000, which was lower than the incidence rate of PBTs worldwide.

Fig. 3
Fig.3Distribution of primary brain tumors based on the anatomical location.Distribution of all primary brain tumors (A), distribution of malignant primary brain tumors (B), and distribution of benign primary brain tumors (C)

Fig. 4
Fig. 4 Distribution of the primary brain tumors by histopathology type

Table 2
Incidence rate by years and sex a per 100,

Table 3
Distribution of cases in age groups and sex groups 6 (1.48%) Fig. 2 Distribution of primary brain tumor cases by age and sex

Table 4
The behavior of the primary brain tumors based on the WHO classification

Table 5
Distribution of the primary brain tumors by the anatomical location a NOS Not Otherwise SpecifiedSite ICD-O

Table 6
Distribution of the primary brain tumors by histopathology

Table 7
First sign or symptom by the behavior of the tumor

Table 8
Mortality rate by other variables